This invention relates to devices and methods for storing and mixing injectants, and to devices and methods for filling an ampoule of a needle-less injector prior to an injection. In particular embodiments, the invention relates to devices and methods for filling an ampoule of a needle-less injector with a medication that must be mixed just prior to administration of an injection, and to the storage of such medication prior to mixing and filling. More particularly, the invention relates to injectable medications wherein one component of the medication is a reagent that is stored in dry form.
A number of medications are maximally effective when mixed immediately prior to administration to a patient. These medications may include multiple liquids, or, alternatively, at least one liquid that is mixed with an active stored in solid form. Generally, the need for mixing immediately prior to injection is due to the rapid loss of medicinal efficacy of a particular reagent included in the medication once the components thereof are combined.
This is often the case with lyophilized actives. Lyophilized actives are essentially freeze-dried pharmaceuticals that do not maintain efficacy when stored for a substantial period of time in solution. In fact, most lyophilized actives become medicinally ineffective once in solution for more than a few hours, and many such actives lose effectiveness after just a few minutes. This rapid loss of medicinal efficacy creates a storage and delivery problem, frequently obviated by storing the lyophilized active in solid form and mixing it with a liquid immediately prior to injection.
The liquid with which a lyophilized active is mixed often adds little therapeutic quality to the final mixture. Rather, the liquid is usually a delivery vehicle, able to carry the otherwise dry active through a needle into the tissue of a patient. Since liquid delivery vehicles present the same efficacy loss problems discussed above, delivery of lyophilized actives by other means has been attempted. For instance, in one system lyophilized actives are coated on the surface of gold particles, and helium gas is used to accelerate these coated particles against and into the skin surface of a patient. This method has several drawbacks, however, as it can be painful to a recipient, and because the lyophilized active may not be delivered to an appropriate segment of a patient""s tissue. Frequently such actives require subdermal delivery, which is not readily achieved by the acceleration method.
In general, a typical injection is performed with a syringe that pierces the skin with a needle to deliver medication to a desired location on a body. Oftentimes, the syringes are pre-filled with a medication. However, if a particular medication does not have a long shelf life, as is generally the case with lyophilized actives in solution, the medication must be mixed just prior to an injection to maintain potency. This requires the medication to be mixed externally to the syringe and then drawn in using needles or the like. After drawing in the medication, the injection may be administered in a normal manner. But, after the injection there are one or more needles that need to be disposed of, increasing both cost and the potential for health hazards from exposure to used needles.
As an alternative to needle delivery injections, needle-less medication injections have been performed with xe2x80x9cpermanent gunxe2x80x9d instruments, generally referred to as xe2x80x9cjet injectors.xe2x80x9d These devices use either a compression spring or a compressed inert gas to propel a fluid medication (via a push rod plunger) through a small orifice (an injector nozzle) which rests perpendicular to and against the injection site. The fluid medication is generally accelerated at a high rate to a speed of between about 800 feet per second (fps) and 1,200 fps (approximately 244 and 366 meters per second, respectively). This causes the fluid to pierce through the skin surface without the use of a needle, resulting in the medication being deposited in a flower pattern under the skin surface.
Reusable jet injectors can accept pre-loaded medication cartridges, but the cartridges must be pre-loaded just prior to an injection for certain medications with short shelf lives. The procedure is to again use a needle and a syringe to mix and then load the medication in the cartridge prior to an injection. After drawing in the medication, the needle-less injection is administered in a normal manner. But, after the injection there are again one or more needles that need to be disposed of, presenting problems of cost and safety, as described above.
Single use needle-less jet injectors offer an alternative to multi-use, needle-less injectors, since they are low cost and can be pre-loaded at the point of manufacture. However, if the medication does not have a long shelf life, the pre-loading is impractical for the same reasons discussed above. Thus, single-use, needle-less injectors have generally not been usable with medications that must be mixed prior to injection. An alternative to overcome this drawback was to include a two compartment ampoule in the injector, which is opened up with a piercing mechanism such that two components are combined together to mix a medication as an injection takes place. Although this obviates the need for needles, the results are unsatisfactory, since the medication is not always thoroughly mixed and properly deposited under the skin. In addition, improper mixing can allow the medication (large molecule medications in particular) to be destroyed or altered during the injection process. Further, the piercing mechanism included in the ampoule may block or obscure the orifice, or jam the needle-less injector leading to an improper injection.
U.S. Pat. No. 6,223,786 and U.S. Pat. No. 6,302,160 describe devices and methods for mixing medications and filling the ampoule of a needle-less injector, thus obviating some of the limitations inherent in using needle-less injectors for the administration of actives with short shelf lives.
It is an object of an embodiment of the present invention to provide an improved device and method for filling an ampoule of a needle-less injector with a mixture that is prepared just prior to administration of an injection, and to the storage of the components of such mixture prior to mixing and filling, that obviates for practical purposes, the above-mentioned limitations.
According to an embodiment of the present invention, an apparatus for preparing a mixture and filling an ampoule of a needle-less injector suitable for injecting the mixture includes an ampoule and a fluid holder. The ampoule may initially contain a dry reagent, and the fluid holder may initially contain a fluid. Preferably, the fluid holder also includes a fluid plunger rod, and the ampoule is coupled to the fluid holder to provide fluid communication therebetween. The fluid plunger rod may be depressed, loading the fluid into the ampoule where it mixes with the dry reagent, thus creating a mixture in the ampoule. In most preferred embodiments, the fluid holder includes a breakable membrane that prevents the fluid from being in communication with the dry reagent until the breakable membrane is broken by the application of pressure upon the fluid plunger rod. In yet further embodiments, the ampoule may include an ampoule plunger rod. After the mixture is prepared, the ampoule plunger rod may be depressed to expel air or gas either into the fluid holder from the ampoule of the needle-less injector, or to the local atmosphere if the fluid holder has already been detached from the ampoule. If the fluid holder has not been detached from the ampoule, the fluid holder plunger rod may be partially withdrawn to pull air or gas from the ampoule into the fluid holder. Most preferably, the mixture of the fluid and the dry reagent is prepared just prior to injection of the mixture due to a short shelf life of the mixture. After mixing and filling is completed, the fluid holder may be detached from the ampoule, the ampoule may be further attached to a needle-less injector and an injection may be administered. In alternate embodiments, the entire housing of a needle-less injector may be the ampoule to which the fluid holder is coupled.
According to another embodiment of the present invention, a method of preparing a mixture and filling an ampoule of a needle-less injector suitable for injecting the mixture includes the steps of: providing an ampoule containing a dry reagent; providing a fluid holder containing a fluid; providing the fluid holder with a fluid plunger rod; coupling the ampoule to the fluid holder to provide fluid communication therebetween; and depressing the fluid plunger rod to load the fluid into the ampoule to mix the fluid and the dry reagent. Further embodiments may include the additional steps of: providing the fluid holder with a breakable membrane; and depressing the fluid plunger rod to rupture the breakable membrane, such that the fluid can be in communication with the dry reagent. Still further embodiments may include the additional steps of providing the ampoule with an ampoule plunger rod; and depressing the ampoule plunger rod after the ampoule is loaded with fluid and the fluid and dry reagent are mixed, to expel air or gas into the fluid holder from the ampoule of the needle-less injector or to the local atmosphere in those instances where the fluid holder and the ampoule have already been detached from one another. If the fluid holder has not been detached from the ampoule, then an embodiment may include the step of: at least partially withdrawing the fluid holder plunger rod to pull air or gas from the ampoule into the fluid holder. Preferably, the step of filling the ampoule thereby creating the mixture of the fluid and the dry reagent occurs just prior to injection of the mixture due to a short shelf life of the mixture. The method may include the step of attaching the ampoule to a needle-less injector after filling the ampoule with the fluid and creating the mixture of the fluid and the dry reagent.
Other features and advantages of the invention will become apparent from the following detailed description, taken in conjunction with the accompanying drawings, which illustrate, by way of example, various features of embodiments of the invention.